I like that idea. Also, progressively *disappearing* resources as they either become "obsolete" / commonplace like dye or spices, or the old silver mines dry up, which drives New World expansion. It would really fit with the Era progression theme to have resources that change over time, and it would help limit resource-bonus bloat as well as put a time limit on the value of trade routes.
A complete system would include the ability to 'move' natural resources like Hoses, Cattle, Sheep, Silk, Dyes, etc to similar terrain/climates elsewhere. In the Neolithic/Ancient where the game starts, in fact, Horses were only native to a single swath of territory from Mongolia across Central Asia to northeastern Europe: they had to be spread, largely by Human action, to the rest of Europe, China, the Middle East, India, and North Africa. Everybody knows that horses were not in t he Americas, they don't realize there were a lot of other places they weren't as well, until people intervened.
Depleting minerals would also have to be part of the system: not only do 'new' deposits of Iron, Gold, Silver, Lead, Coal, Oil, etc. show up, but old ones get depleted or "worked out", while new ones replace them - frequently in some other region.
And finally, many 'natural' Resources get replaced. Natural Dyes now are a niche, craft market: the invention of artificial coal tar or aniline dyes in the 1850s completely replaced them for most commercial purposes. manufactured Luxuries should replace a great many of the natural ones by the Industrial and Modern Ages - the value of modern Trade Routes in Porcelain or Papyrus is negligible compared to the Trade in Automobiles, Machine Tools, or Personal Electronics.
(Though the New World in HK is even worse than in Civ - if you're there first you can just claim the whole lot with outposts and every-improvement-built cities, and the independents are no match for Arquebuses. To make the New World interesting it maybe needs an arbitrary limitation so that you can have a proper, fair, scramble - like in Victoria 2 where nobody can colonize Africa until 1840, and then every Great Power can immediately).
The historical constraints on wide-spread colonization in the Americas were two: Tropical disease in the first settlements in the Caribbean, southern North America and South America killed off up to 90% of the European colonists, and kept killing them as fast as they could arrive for generations (as far north as Jamestown, Virginia, which was placed in a coastal swamp full of malarial mosquitos - smart move), and Colonists and colonies a long way from the Mother Country in distance and time tended to get Independent in deed if not legal fact pretty quickly. In game terms, perhaps a massive Stability Hit to any Outpost or City founded on a different continent or in a different Hemisphere, or a massive Influence cost coupled with a massive Money maintenance cost for every region settled in a different Hemisphere - the map selection options in game set-up includes the Hemisphere concept, so it's coded in there somewhere already.